Rules for modeling signal-transduction systems.
Rules for modeling signal-transduction systems.
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DOI：
10.1126/stke.3442006re6
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发表时间：
2006-07-18
期刊：
影响因子：
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通讯作者：
Fontana, Walter
中科院分区：
文献类型：
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作者：
Hlavacek, William S;Faeder, James R;Fontana, Walter
最近引入了蛋白质 - 蛋白质相互作用的形式规则，以代表细胞信号中蛋白质的结合和酶促活性。规则编码了对系统如何起作用的理解，该系统在系统中的生物分子及其可能的状态和相互作用方面。一组规则可以像图解的互动图一样容易阅读，但是与大多数此类地图不同，规则具有精确的解释。可以处理规则以自动为系统生成数学或计算模型，从而可以对系统行为进行解释性和预测性见解。规则是促进模型修订的模型规范的独立单位。在常规数学模型的情况下，可以简单地通过添加或更改代表感兴趣相互作用的单个规则来引入或修改蛋白质相互作用，而不是更改大量方程或代码行，而是可以进行蛋白质相互作用。可以通过使用图来定义和可视化规则，因此对于创建模型或利用规则的代表性精度，数学或计算机科学的专业培训是必需的。可以以机器可读的格式编码规则，以实现电子存储和模型交换，以及有关蛋白质 - 蛋白质相互作用的基本知识。在这里，我们回顾了基于规则的建模的动机；该方法的应用；以及模型规范，仿真和测试中出现的问题。我们还讨论了规则可视化和交换以及可用于基于规则的建模的软件。
Formalized rules for protein-protein interactions have recently been introduced to represent the binding and enzymatic activities of proteins in cellular signaling. Rules encode an understanding of how a system works in terms of the biomolecules in the system and their possible states and interactions. A set of rules can be as easy to read as a diagrammatic interaction map, but unlike most such maps, rules have precise interpretations. Rules can be processed to automatically generate a mathematical or computational model for a system, which enables explanatory and predictive insights into the system's behavior. Rules are independent units of a model specification that facilitate model revision. Instead of changing a large number of equations or lines of code, as may be required in the case of a conventional mathematical model, a protein interaction can be introduced or modified simply by adding or changing a single rule that represents the interaction of interest. Rules can be defined and visualized by using graphs, so no specialized training in mathematics or computer science is necessary to create models or to take advantage of the representational precision of rules. Rules can be encoded in a machine-readable format to enable electronic storage and exchange of models, as well as basic knowledge about protein-protein interactions. Here, we review the motivation for rule-based modeling; applications of the approach; and issues that arise in model specification, simulation, and testing. We also discuss rule visualization and exchange and the software available for rule-based modeling.